Cancer and infectious disease take a considerable toll on our society in terms of morbidity and mortality. The competence of the immune system is an important factor in the pathogenesis of these conditions, and current work suggests that relationships exist between emotional states (especially depression) and impared immune functioning. The long-term objectives of the proposed work is to further investigate this interaction between the central nervous system and immune system, focusing on how the psychiatric disorders impact upon immune competence. Initially, special attention will be paid to the depressive disorder. The present study is designed to test the following hypotheses: 1) Patients with a Major Depressive Disorder (MDD) defined by Research Diagnostic Criteria (RDC) will have an impaired (altered) immune status as compared to non-depressed, healthy controls, 2) The altered immune status will be associated with those depressed patients who exhibit plasma hypercortisolemia, and 3) The altered immune status will be a function of the "state" of the depressed individual; not a "trait" function (i.e., the alteration will disappear upon resolution of the depression). To accomplish the goal, immunologic function and cortisol secretion will be measured in twenty hospitalized and twenty clinic patients diagnosed with MDD by RDC criteria. All forty patients will be age, sex and race-matched with normal controls. Immunologic function will be measured by using Natural Killer Cell Activity (NKCA) assays, lymphocyte proliferative assays, and Delayed Cutaneous Hypersensitivity (DCH) reactions. Cortisol secretion will be assessed by serial serum measures taken over a 3-hour period. To examine the hypothesis that altered immune competence in depression is a function of the depressed state (like plasma hypercortisolemia), patients will be studied longitudinally; before treament, during treatment, and upon recovery. Assessment of lymphocyte proliferation, NKCA, and DCH in depressed individuals will be relevant to a further understanding of previously reported relationships between depression and somatic illness. Furthermore, if a relationship between hypercortisolemia and impaired immunity is uncovered, we may then be able to identify a population of individuals at increased risk for morbidity. Additional work in this area will further characterize any observed alterations in immune function as well as further characterize the subjects who show these alterations.